3D cell culture: Making cells feel right at home

Houston 15 March 2010The film "Avatar" isn't the only 3D blockbuster making a splash this winter. A team of Houston scientists has unveiled a new technique for growing 3D cell cultures, a technological leap from the flat petri dish that could save millions of dollars in drug-testing costs. The research is reported in Nature Nanotechnology. The 3-dimensional technique is easy enough for most labs to set up immediately. It uses magnetic forces to levitate cells while they divide and grow. Compared with cell cultures grown on flat surfaces, the 3D cell cultures tend to form tissues that more closely resemble those inside the body.


"There's a big push right now to find ways to grow cells in 3D because the body is 3D, and cultures that more closely resemble native tissue are expected to provide better results for preclinical drug tests", stated study co-author Tom Killian, Ph.D., associate professor of physics at Rice University. "If you could improve the accuracy of early drug screenings by just 10 percent, it's estimated you could save as much as $100 million per drug."

For cancer research, the "invisible scaffold" created by the magnetic field goes beyond its potential for producing cell cultures that are more reminiscent of real tumours, which itself would be an important advance, said co-author Wadih Arap, M.D., Ph.D., professor in the David H. Koch Center at the University of Texas M.D. Anderson Cancer Center.

To make cells levitate, the research team modified a combination of gold nanoparticles and engineered viral particles called "phage" that was developed in the lab of Wadih Arap and Renata Pasqualini, Ph.D., also of the Koch Center. This targeted "nanoshuttle" can deliver payloads to specific organs or tissues. "A logical next step for us will be to use this additional magnetic property in targeted ways to explore possible applications in the imaging and treatment of tumours", Wadih Arap stated.

The 3D modelling raises another interesting long-term possibility. "This is a step toward building better models of organs in the lab", Renata Pasqualini stated.

The new technique is an example of the innovation that can result when experts come together from disparate fields. Tom Killian studies ultracold atoms and uses finely tuned magnetic fields to manipulate them. He had been working with Rice bio-engineer Robert Raphael, Ph.D., for several years on methods to use magnetic fields to manipulate cells. So when Tom Killian's friend Glauco Souza, Ph.D., then an Odyssey Scholar studying with Wadih Arap and Renata Pasqualini, mentioned that he was developing a gel that could load cancer cells with magnetic nanoparticles, it led to a new idea.

"We wondered if we might be able to use magnetic fields to manipulate the cells after my gels put magnetic nanoparticles into them", stated Glauco Souza, who left M.D. Anderson in 2009 to co-found Nano3D Biosciences, a start-up that subsequently licensed the technology from Rice and M.D. Anderson.

The nanoparticles in this case are tiny bits of iron oxide. These are added to a gel that contains phage. When cells are added to the gel, the phage causes the particles to be absorbed into cells over a few hours. The gel is then washed away, and the nanoparticle-loaded cells are placed in a petri dish filled with a liquid that promotes cell growth and division.

In the new study, the researchers showed that by placing a coin-sized magnet atop the dish's lid, they could lift the cells off the bottom of the dish, concentrate them and allow them to grow and divide while they were suspended in the liquid.

A key experiment was performed in collaboration with Jennifer Molina, a graduate student in the laboratory of Maria-Magdalena Georgescu, Ph.D., an associate professor in M.D. Anderson's Department of Neuro-Oncology, in which the technique was used on brain tumour cells called glioblastomas. The results showed that cells grown in the 3D medium produced proteins that were similar to those produced by gliobastoma tumours in mice, while cells grown in 2D did not show this similarity.

Glauco Souza said that Nano3D Biosciences is conducting additional tests to compare how the new method stacks up against existing methods of growing 3D cell cultures. He said he is hopeful that it will provide results that are just as good, if not better, than longstanding techniques that use 3D scaffolds.

Robert Raphael, a paper co-author, associate professor in bio-engineering and a member of Rice's BioScience Research Collaborative, stated: "The beauty of this method is that it allows natural cell-cell interactions to drive assembly of 3D microtissue structures. The method is fairly simple and should be a good point of entry in 3D cell culturing for any lab that's interested in drug discovery, stem cell biology, regenerative medicine or biotechnology."

Other co-authors include Daniel Stark, Ph.D., and Jeyarama Ananta, Ph.D., both of Rice; Carly Levin, Ph.D., of Nano3D Biosciences; and Michael Ozawa, Lawrence Bronk, Jami Mandelin, Ph.D., of the Koch Center and M. D. Anderson's Department of Genitiourinary Medical Oncology, James Bankson, Ph.D., of M. D. Anderson's Department of Imaging Physics, and Juri Gelovani, M.D., Ph.D., of M. D. Anderson's Department of Experimental Diagnostic imaging.

Michael Ozawa and Lawrence Bronk are graduate students at the University of Texas Graduate School of Biomedical Sciences at Houston, a joint programme of M. D. Anderson and the University of Texas Health Science Center at Houston (UTHealth).

The research was funded by M.D. Anderson's Odyssey Scholar Programme, the Department of Defense's Breast Cancer Research Programme, the National Science Foundation, the Packard Foundation, the Gillson-Longenbaugh Foundation, AngelWorks, the National Institutes of Health and the National Cancer Institute.

The University of Texas M. D. Anderson Cancer Center and its researchers have filed patents on the technology and other intellectual property reported in these papers. If licensing or commercialization of such intellectual property occurs, the researchers and M. D. Anderson may be entitled to financial consideration, including royalties. M. D. Anderson manages these relationships in accordance with appropriate statutes, rules, regulations and policies.

Located in Houston, Rice University is consistently ranked one of America's best teaching and research universities. Known for its "unconventional wisdom", Rice is distinguished by its: size - 3102 undergraduates and 2237 graduate students; selectivity - 12 applicants for each place in the freshman class; resources - an undergraduate student-to-faculty ratio of 5-to-1; sixth largest endowment per student among American private research universities; residential college system, which builds communities that are both close-knit and diverse; and collaborative culture, which crosses disciplines, integrates teaching and research, and intermingles undergraduate and graduate work.

The University of Texas M.D. Anderson Cancer Center in Houston ranks as one of the world's most respected centres focused on cancer patient care, research, education and prevention. M.D. Anderson is one of only 41 Comprehensive Cancer Centres designated by the National Cancer Institute. For four of the past six years, M.D. Anderson has ranked no. 1 in cancer care in "America's Best Hospitals", a survey published annually in U.S. News and World Report.

Source: University of Texas M.D. Anderson Cancer Center

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